Introduction: We assessed the clinical validity of circulating tumour cell (CTC) quantification for prognostication of patients with advanced non-small cell lung cancer (NSCLC) by undertaking a pooled analysis of individual patient data. Methods: Nine European NSCLC CTC centres were asked to provide reported/unreported pseudo-anonymised data for patients with advanced NSCLC who participated in CellSearch CTC studies from January 2003 to March 2017. We used Cox regression models, stratified by centres, to establish the association between CTC count and survival. We assessed the added value of CTCs to prognostic clinicopathological models using likelihood ratio (LR) statistics and c-indices. Results: Seven out of nine eligible centres provided data for 550 patients with prognostic information for overall survival. CTC counts of ≥2 and ≥ 5 per 7·5 mL were associated with reduced progression-free survival (≥2 CTCs: hazard ratio [HR] = 1.72, p < 0·001; ≥5 CTCs: HR = 2.21, p < 0·001) and overall survival (≥2 CTCs: HR = 2·18, p < 0·001; ≥5 CTCs: HR = 2·75, p < 0·001), respectively. Survival prediction was significantly improved by addition of baseline CTC count to LR clinicopathological models (log-transformed CTCs p < 0·001; ≥2 CTCs p < 0·001; ≥5 CTCs p ≤ 0·001 for both survival end-points), whereas moderate improvements were observed with the use of c-index models. There was some evidence of between-centre heterogeneity, especially when examining continuous counts of CTCs. Conclusions: These data confirm CTCs as an independent prognostic indicator of progression-free survival and overall survival in advanced NSCLC and also reveal some evidence of between-centre heterogeneity. CTC count improves prognostication when added to full clinicopathological predictive models.

EPAC-lung: pooled analysis of circulating tumour cells in advanced non-small cell lung cancer / Lindsay, C. R.; Blackhall, F. H.; Carmel, A.; Fernandez-Gutierrez, F.; Gazzaniga, P.; Groen, H. J. M.; Hiltermann, T. J. N.; Krebs, M. G.; Loges, S.; Lopez-Lopez, R.; Muinelo-Romay, L.; Pantel, K.; Priest, L.; Riethdorf, S.; Rossi, E.; Terstappen, L.; Wikman, H.; Soria, J. -C.; Farace, F.; Renehan, A.; Dive, C.; Besse, B.; Michiels, S.. - In: EUROPEAN JOURNAL OF CANCER. - ISSN 0959-8049. - 117:(2019), pp. 60-68. [10.1016/j.ejca.2019.04.019]

EPAC-lung: pooled analysis of circulating tumour cells in advanced non-small cell lung cancer

Gazzaniga P.
Membro del Collaboration Group
;
2019

Abstract

Introduction: We assessed the clinical validity of circulating tumour cell (CTC) quantification for prognostication of patients with advanced non-small cell lung cancer (NSCLC) by undertaking a pooled analysis of individual patient data. Methods: Nine European NSCLC CTC centres were asked to provide reported/unreported pseudo-anonymised data for patients with advanced NSCLC who participated in CellSearch CTC studies from January 2003 to March 2017. We used Cox regression models, stratified by centres, to establish the association between CTC count and survival. We assessed the added value of CTCs to prognostic clinicopathological models using likelihood ratio (LR) statistics and c-indices. Results: Seven out of nine eligible centres provided data for 550 patients with prognostic information for overall survival. CTC counts of ≥2 and ≥ 5 per 7·5 mL were associated with reduced progression-free survival (≥2 CTCs: hazard ratio [HR] = 1.72, p < 0·001; ≥5 CTCs: HR = 2.21, p < 0·001) and overall survival (≥2 CTCs: HR = 2·18, p < 0·001; ≥5 CTCs: HR = 2·75, p < 0·001), respectively. Survival prediction was significantly improved by addition of baseline CTC count to LR clinicopathological models (log-transformed CTCs p < 0·001; ≥2 CTCs p < 0·001; ≥5 CTCs p ≤ 0·001 for both survival end-points), whereas moderate improvements were observed with the use of c-index models. There was some evidence of between-centre heterogeneity, especially when examining continuous counts of CTCs. Conclusions: These data confirm CTCs as an independent prognostic indicator of progression-free survival and overall survival in advanced NSCLC and also reveal some evidence of between-centre heterogeneity. CTC count improves prognostication when added to full clinicopathological predictive models.
2019
Circulating tumour cells; CTCs; KRAS; Lung cancer; Non-small cell
01 Pubblicazione su rivista::01a Articolo in rivista
EPAC-lung: pooled analysis of circulating tumour cells in advanced non-small cell lung cancer / Lindsay, C. R.; Blackhall, F. H.; Carmel, A.; Fernandez-Gutierrez, F.; Gazzaniga, P.; Groen, H. J. M.; Hiltermann, T. J. N.; Krebs, M. G.; Loges, S.; Lopez-Lopez, R.; Muinelo-Romay, L.; Pantel, K.; Priest, L.; Riethdorf, S.; Rossi, E.; Terstappen, L.; Wikman, H.; Soria, J. -C.; Farace, F.; Renehan, A.; Dive, C.; Besse, B.; Michiels, S.. - In: EUROPEAN JOURNAL OF CANCER. - ISSN 0959-8049. - 117:(2019), pp. 60-68. [10.1016/j.ejca.2019.04.019]
File allegati a questo prodotto
File Dimensione Formato  
Lindsay_EPAC-lung_2019.pdf

accesso aperto

Tipologia: Documento in Post-print (versione successiva alla peer review e accettata per la pubblicazione)
Licenza: Tutti i diritti riservati (All rights reserved)
Dimensione 1.17 MB
Formato Adobe PDF
1.17 MB Adobe PDF

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1297994
Citazioni
  • ???jsp.display-item.citation.pmc??? 38
  • Scopus 58
  • ???jsp.display-item.citation.isi??? 54
social impact